A multiparametric approach utilized to study the interaction of Trypanosoma cruzi with vertebrate cells indicates that the infection of vertebrate cells by T. cruzi is an active process. Cytochalasin does not inhibit the infection of non-phagocytic vertebrate cells by trypomastigotes. Chronic chagasic serum enhances the ability of trypomastigotes to penetrate vertebrate cells. The phenomenon is not specific to parasite strain, host cell type or serum source. Total immunoglobins are capable of enhancing penetration. However, purified specific immunoglobulin fractions are inactive. Activity is restored to the IgG fraction with an as yet undefined factor present in normal human serum. The first round of DNA synthesis by a population of intracellular amastigotes is synchronous. Synchrony decays during subsequent parasite divisions. The confirmation of a lag period prior to the initial round of DNA synthesis indicates that trypomastigotes are in an extended G1 (Go) phase prior to infection of a vertebrate cell. A group of vetebrate cell X T. cruzi hybrids have been produced utilizing P3-X63Ag8 vertebrate cells and T. cruzi epimastigotes. The vertebrate cell hybrids express T. cruzi antigen as demonstrated by IFA. Antigen expression has been stable for 14 weeks.